HER2-positive breast cancer: Current and future treatment strategies

In the year 2006, breast cancer was estimated to affect >200 000 American women and cause nearly 56 000 deaths. Furthermore, breast cancer is the most common cancer diagnosed and second most common cause of cancer-related deaths in women. The current treatment armamentarium for breast cancer includes chemotherapy, endocrine therapy and biological therapy. Treatment has become more individualised based on characteristics of the tumour including overexpression of the human epidermal growth factor receptor (HER)-2. Between 20 and 30% of all breast cancers overexpress HER2, which means 40 000-60 000 patients will have this type of cancer. Previously, overexpression of HER2 was a negative prognostic and predictive risk factor for survival; however, with the advent of trastuzumab, patients' prognosis is improving in all treatment settings. Much controversy exists in the use of trastuzumab, including (i) the sequence of adjuvant trastuzumab (concurrent with chemotherapy or sequential); (ii) the treatment duration (<1 year, 1 year or 2 years); and (iii) the treatment choice upon disease progression (whether to continue or not with trastuzumab and add another cytotoxic agent). Current trials are ongoing to help answer these questions. Furthermore, there has been interest in predicting which HER2-positive patients would require anthracycline therapy, and which could avoid anthracycline therapy and its toxicities. Novel therapeutics, such as lapatinib, an oral tyrosine kinase inhibitor, which blocks both the epidermal growth factor receptor and HER2 receptor has recently been approved by the US FDA. Whereas pertuzumab, a humanised monoclonal antibody, directed against heterodimerisation of HER2 and HER3 has entered phase II and III clinical trials.